In the United States there are currently no regulations regarding the sterilization requirements of topical antiseptic solutions. Therefore, antiseptic solutions currently sold in the United States generally do not undergo a sterilization process. In other jurisdictions, however, such as European Union (EU) countries, some degree of sterilization is required. A known antiseptic solution containing 2% w/v chlorhexidine gluconate in 70% v/v isopropanol in water, manufactured by CareFusion Corp., is sterilized for EU countries using a known sterilization method.
The known method of sterilization involves heat treating glass ampoules containing the chlorhexidine gluconate solution in a convection oven at 76-80° C. for 24-31 hours. It is currently believed that relatively low temperature and relatively long processing time is necessary to sufficiently sterilize the solution without overly degrading the antimicrobial molecules, thereby avoiding reducing the concentration and purity of the chlorhexidine gluconate contained therein as an antiseptic. Degrading the antimicrobial molecules creates undesired impurities as well as lowers the overall concentration of the active drug moiety. Regulations in the United States and EU countries limit the amount of impurities that may be present in the antiseptic solution. Furthermore, a convection oven, which utilizes air to conduct heat, is an inefficient process because the initial heating of the solution from room temperature (also referred herein as “ramp up” time) and eventual cooling down of the solution back to room temperature (also referred herein as “cool down” time) is relatively long. For example the ramp up time for the solution to reach the sterilization temperature can be 2-6 hours while the cool down period can be 1-2 hours. Accordingly, the time that the chlorhexidine gluconate solution is exposed to the sterilizing temperature (i.e., the time at 76-80° C.) in the known method can be 22 to 24 hours, while the total processing time (i.e., including ramp up, sterilization and cool down time) may be around 25 to 32 hours.
It is the industry belief that high temperature sterilization is not suitable due to the expected degradation. See, for example, Kelly M. Pyrek, “Sterility of Antiseptic Products: FDA Investigates, Deliberates on Potential Recommendations,” Infection Control Today (July 2013): 24-26 and Block, Seymour S. Disinfection, Sterilization, and Preservation. Philadelphia: Lippincott Williams & Wilkens, 322-323. 2001.
Thus, there is an unmet need in the art for a method of sterilizing antiseptic solutions that has a shorter, more efficient processing time, and provides a sterile solution while maintaining sufficient purity of the antiseptic solution to comply with regulatory requirements.